Robustness and evolution: concepts, insights and challenges from a developmental model system. Marie-Anne Félix, A. Wagner To cite this version: Marie-Anne Félix, A. Wagner. Robustness and evolution: concepts, insights and challenges from a developmental model system.. Heredity, Nature Publishing Group, 2006, sous presse, 10.1038/sj.hdy.6800915. hal-00134296 HAL Id: hal-00134296 https://hal.archives-ouvertes.fr/hal-00134296 Submitted on 1 Sep 2007 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. This is an author-prepared PDF of a manuscript published in Heredity (2006) doi:10.1038/sj.hdy.6800915 Robustness and evolution: concepts, insights, and challenges from a developmental model system Marie-Anne Félix1 and Andreas Wagner2 1Institut Jacques Monod, CNRS-Universities of Paris 6/7, Tour 43, 2 place Jussieu, 75251 Paris cedex 05, France. [email protected] 2 University of Zurich, Dept. of Biochemistry, Bldg. Y27, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. [email protected] Abstract Robustness, the persistence of an organismal trait under perturbations, is a ubiquituous property of complex living systems. We here discuss key concepts related to robustness with examples from vulva development in the nematode Caenorhabditis elegans. We emphasize the need to be clear about the perturbations a trait is (or is not) robust to. We discuss two prominent mechanistic causes of robustness, namely redundancy and distributed robustness. We also discuss possible evolutionary causes of robustness, one of which does not involve natural selection. To better understand robustness is of paramount importance for understanding organismal evolution. Part of the reason is that highly robust systems can accumulate cryptic variation that can serve as a source of new adaptations and evolutionary innovations. We point to some key challenges in improving our understanding of robustness. Introduction Robustness is important in ensuring the stability of phenotypic traits which are constantly Here we first define robustness and review exposed to genetic and non-genetic variation. To experimental ways to detect it. We then discuss the better understand robustness is of paramount proximate mechanisms underlying robustness. We importance for understanding organismal finally discuss evolutionary causes and evolution, because robustness permits cryptic consequences of robustness. genetic variation to accumulate. Such variation may serve as a source of new adaptations and What is robustness, and why is it important? evolutionary innovations. We will here focus on developmental traits Robustness is the persistence of an organismal and on the robust formation of organs. Specifically, trait under perturbations. Many different we will discuss important concepts and challenges organismal features could qualify as traits in this in studying robustness using the vulva of the definition of robustness. A trait could be the proper nematode C. elegans, an exceptionally well-studied fold or activity of a protein, a gene expression developmental model. Here, the robust trait is the pattern produced by a regulatory gene network, the spatial pattern of vulval cell fates (Box 1). For regular progression of a cell division cycle, the further reading on different aspects of biological communication of a molecular signal from cell robustness and canalization, a non-exhaustive list surface to nucleus, a cell interaction necessary for of more extensive reviews includes: Gibson and embryogenesis, or the proper formation of a viable Wagner 2000; Debat and David 2001; de Visser et organism or organ. al. 2003; Gibson and Dworkin 2004; Flatt 2005; Wagner 2005a; Dworkin 2005a. 1 This is an author-prepared PDF of a manuscript published in Heredity (2006) doi:10.1038/sj.hdy.6800915 We note that the final product of a changes. In contrast, some traits are strongly biological process may be robust despite variation influenced by the environment, for example the in some intermediate trait (Fig. 1), such as a propensity of C. elegans larvae to develop through developmental stage, the activity of a signaling the resistant dauer stage (Riddle and Albert 1997). pathway, or the expression of a gene product. To The effect of the environment may range from a give but one example from vulval development, shift in a quantitative distribution (for example animals that are heterozygotes for a null mutation body size as a function of nutrition in humans) to in the gene coding for the EGF signal have a the appearance of alternative phenotypes (for normal vulva fate pattern (Ferguson and Horvitz example caste determination as a function of 1985). This indicates that variation in EGF signal nutrition in social insects). In these cases, the final levels – which can be viewed as an intermediate phenotype is not robust, but plastic (Pigliucci phenotypic trait – is buffered. Cell fate output is 2005). The ecology of an organism is thus clearly invariant to such buffered variation. important to understanding a trait’s robustness properties. Specifically, robustness to frequent environmental perturbations may be of greater Robustness to what? adaptive significance than robustness to perturbations that occur rarely or never. Robustness can be discussed sensibly only if two The third kind of perturbation is genetic cardinal questions have been resolved. What is the change, either through de novo mutation or through trait of interest? And what is the perturbation of recombination. Here, the genetic structure of interest? There are three principal kinds of populations becomes relevant to characterize perturbations to which a system may be robust: robustness properties. As a simple example, in stochastic noise, environmental change, and diploids the effect of a new recessive mutation will genetic variation (Fig. 1). depend on its probability to be found in the Noise refers to the stochastic fluctuations homozygous state. This probability itself is a that occur in any biological system, for example in function of the mode of reproduction (selfing the concentration of a biological molecule or in a versus outcrossing) and of the effective size of the cell’s position, either over time, or between two population (Hartl and Clark 1997). In addition to genetically identical individuals, even if the mutational variation, robustness to genetic external environment is constant. Developmental variation includes robustness to the effect of traits lacking robustness to noise include human recombination between alleles at different loci. As fingerprints, which differ among genetically a consequence, spatial genetic structure becomes identical twins (Stigler 1995). An example from C. crucial in the evolution of a system’s robustness elegans vulval development is the division pattern properties, for example through the migration rate of the cell P3.p at the anterior border of the vulva between populations adapted to local environments competence group (see Box). This cell divides in (Ancel Meyers and Bull 2002; Proulx and Phillips only some genetically identical worms, whereas in 2005). Frequent recombination may favor the others it directly fuses with the epidermal evolution of mutational robustness. This form of syncytium and loses vulval competence (Sulston genetic robustness may result in negative epistasis and Horvitz 1977; Eisenmann et al. 1998). (synthetic effects of deleterious mutations), which The second kind of perturbation is variation in turn renders sex (and recombination) in the external environment, for example a change advantageous. This feedback between genetic in temperature, salinity or nutrient availability. robustness and recombination frequency has been Many developmental traits, such as the C. elegans proposed as an explanation for the evolution and vulva fate pattern (C. Braendle and M.-A. F., maintenance of sex (Azevedo et al. 2006). unpublished), are highly robust to environmental 2 This is an author-prepared PDF of a manuscript published in Heredity (2006) doi:10.1038/sj.hdy.6800915 precise and robust to stochastic noise (Delattre and How is robustness detected? Félix 2001; C. Braendle and M.-A. F., unpublished). The degree of robustness and the Robustness is not an all-or-nothing property. It is a types of error can be compared between different matter of degree. For a quantitative trait, lack of isogenic backgrounds. A second way to eliminate robustness can be expressed using the coefficient confounding effects from genetic variation in of variation (square root of the variance over the measuring robustness to noise is to quantify the mean) for the trait or, when comparing two developmental variation between the right and left conditions, the unsigned difference in the means sides of an animal (fluctuating asymmetry). (Dworkin 2005a). For a complex qualitative trait Robustness of a trait to environmental such as a protein sequence or the vulval cell fate variation is detected by subjecting organisms to a pattern, robustness (or a lack thereof) can be given environmental change or an array of expressed